Chain Mediation Analysis of the Effects of Nutrition and Cognition on the Association of Apolipoprotein E ɛ4 with Neuropsychiatric Symptoms in Alzheimer’s Disease

Article type: Research Article

Authors: Jiang, Jiwei^{a; b; 1} | Hong, Yin^{c; 1} | Li, Wenyi^{a; b} | Wang, Anxin^{a; b} | Jiang, Shirui^{a; b} | Jiang, Tianlin^{a; b} | Wang, Yanli^{a; b} | Wang, Linlin^{a; b} | Yang, Shiyi^{a; b} | Ren, Qiwei^{a; b} | Zou, Xinying^{a; b} | Xu, Jun^{a; b; *}

Affiliations: [a] Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Fengtai District, Beijing, China | [b] National Clinical Research Center for Neurological Diseases, Fengtai District, Beijing, China | [c] Department of Health Management, Beijing Tian Tan Hospital, Capital Medical University, Fengtai District, Beijing, China

Correspondence: [*] Correspondence to: Jun Xu, PhD, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, National Clinical Research Center for Neurological Diseases, 119 South Fourth Ring Road, Fengtai District, Beijing City 100071, China. Tel.: +010 +59975031; Fax: +86 + 010 + 59975031; E-mail: neurojun@126.com.

Note: [1] These authors contributed equally to this work.

Abstract: Background:Apolipoprotein E (APOE) is the most recognized risk gene for cognitive decline and clinical progression of late-onset Alzheimer’s disease (AD); nonetheless, its association with neuropsychiatric symptoms (NPSs) remains inconclusive. Objective:To investigate the association of APOE ɛ4 with NPSs and explore nutritional status and cognition as joint mediators of this association. Methods:Between June 2021 and October 2022, patients with amnestic mild cognitive impairment (aMCI) or AD were recruited from the Chinese Imaging, Biomarkers, and Lifestyle Study. NPSs were assessed using the Neuropsychiatric Inventory, while global cognition and nutritional status were evaluated using the Mini-Mental State Examination (MMSE) and Mini-Nutritional Assessment (MNA), respectively. Simple mediation and multiple chain mediation models were developed to examine the mediating effects of the MNA and MMSE scores on the relationship between APOE ɛ4 and specific neuropsychiatric symptom. Results:Among 310 patients, 229 (73.87%) had NPSs, and 110 (35.48%) carried APOE ɛ4. Patients with APOE ɛ4 were more likely to have hallucinations (p = 0.014), apathy (p = 0.008), and aberrant motor activity (p = 0.018). MNA and MMSE scores mediated the association between APOE ɛ4 and hallucinations (17.97% and 37.13%, respectively), APOE ɛ4 and apathy (30.73% and 57.72%, respectively), and APOE ɛ4 and aberrant motor activity (17.82% and 34.24%), respectively. Chain-mediating effects of MNA and MMSE scores on the association of APOE ɛ4 with hallucinations, apathy, and aberrant motor activity after adjusting for confounding factors were 6.84%, 11.54%, and 6.19%, respectively. Conclusion: Nutritional status and cognition jointly mediate the association between APOE ɛ4 and neuropsychiatric symptoms in patients with aMCI or AD.

Keywords: Alzheimer’s disease, cognition, mediation analysis, mild cognitive impairment, neuropsychiatric symptoms, nutrition

DOI: 10.3233/JAD-230577

Journal: Journal of Alzheimer's Disease, vol. 96, no. 2, pp. 669-681, 2023